Hapten-induced colitis is associated with colonic patch hypertrophy and T helper cell 2-type responses

To investigate the potential involvement of T helper (Th)2-type responses i n murine models of intestinal inflammation, we used trinitrobenzene sulfoni c acid (TNBS)-hapten to induce inflammatory bowel disease in situations whe re Th1-type responses with interferon (IFN)-gamma synthesis are either dimi nished or do not occur. Intracolonic administration of TNBS to either norma l (IFN-gamma(+/+)) or Th1-deficient IFN-gamma knockout (IFN-gamma(-/-)) BAL B/c mice resulted in significant colitis. In IFN-gamma(-/-) mice, crypt inf lammation was more severe than in IFN-gamma(+/+) mice and was accompanied b y hypertrophy of colonic patches with a lymphoepithelium containing M cells and distinct B and T cell zones resembling Peyer's patches. Hapten-specifi c, colonic patch T cells from both mouse soups exhibited a Th2 phenotype wi th interleukin (IL)-4 and IL-5 production. TNBS colitis in normal mice trea ted with anti-IL-4 antibodies or in IL-4(-/-) mice was less severe than in either IFN-gamma(+/+) or IFN-gamma(-/-) mice. Our findings now show that th e Th2-type responses in TNBS colitis are associated with colonic patch enla rgement and inflammation of the mucosal layer and may represent a model for ulcerative colitis.